key: cord-0929068-nzl2jfza authors: Pessoa, Natália Lima; Diniz, Lilian Martins Oliveira; Andrade, Adriana de Souza; Kroon, Erna Geessien; Bentes, Aline Almeida; Campos, Marco Antônio title: Children with sickle cell disease and severe COVID‐19 presenting single nucleotide polymorphisms in innate immune response genes – A case report date: 2021-11-24 journal: EJHaem DOI: 10.1002/jha2.325 sha: 311f60ef02a5d5661b738341ed5b6909a8786d70 doc_id: 929068 cord_uid: nzl2jfza Here we report three clinical cases of children with sickle cell disease (SCD) and severe COVID‐19 who evolved with complications during hospitalization or after discharge. They present single nucleotide polymorphisms in tlr‐7 and tirap genes, identified from 37 patients under 16 years old hospitalized from September 2020 to May 2021 in the Hospital João Paulo II, Belo Horizonte, Brazil. They presented significant complications of SCD as acute chest syndrome, splenic sequestration, and pain crisis during hospitalization or up to 2 months after SARS‐CoV‐2 infection. They all required transfusion of concentrated red blood cells and hospitalization in a reference hospital to care for children with SCD. SARS-CoV-2 is a single-stranded RNA betacoronavirus responsible for the COVID-19 pandemic. Studies in children infected with SARS-CoV-2 in developed countries have detected low mortality. However, a recent study found that children and adolescents who had a previous disease, such as SCD, had a 2.96 risk of evolving to death [4] . The host's innate immune system is responsible for protecting against microorganisms [5, 6] , including viruses [7] [8] [9] , and there is a recognition of pathogen-associated molecular patterns through their pattern recognition receptors [5] [6] [7] [8] [9] [10] . TLR-7 is a pattern recognition receptor that recognizes single-stranded RNA [10] . Most TLR signaling initiates with the activation of adaptor protein MyD88, which is recruited to the Tir domain present in the cytosolic tail of all TLRs. In response to natural activators of innate immunity, the sorting adaptor Tir domain-containing adaptor protein regulates TLR signaling from the plasma membrane and endosomes [11] . Single nucleotide polymorphisms (SNPs) in innate immune system genes can negatively influence the immune response to infectious diseases [12] , as exemplified by rs179008 (tlr-7) [12] and rs8177374 (tirap) [13] . Chromosomal X tlr-7 loss-of-function variants were identified in four young men with severe COVID-19 [14] . Here we report three clinical cases of children with SCD and severe COVID-19 who evolved with complications during hospitalization or after discharge (Table 1) . These patients with SCD, SARS-CoV-2 positive, with SNPs present in tlr-7 and tirap genes, were identified over 9 months (from September 2020 to May 2021) in the Hospital João Paulo II, Belo Horizonte, Brazil, from 37 cases of severe COVID-19 studied. The identified SNPs rs179008 in the tlr-7 gene and rs8177374 in the tirap gene were tested using the methods described before [15] . with significant pallor associated with splenomegaly (palpable spleen 6 cm from the right costal margin). A total blood count showed a drop in hemoglobin from 8.5 to 6.3 mg/dl, with no reticulocyte increase (0.1%). She received red blood cell transfusions, with gradual improvement, and oxygen therapy was discontinued 3 days later. She was discharged after 11 days of hospitalization. The SNP rs179008 in the tlr-7 gene was identified in this patient. The second patient, a child aged 1 year and 5 months, was admitted to the hospital after 3 days of coughing, fever, and sore throat. He evolved with diarrhea and pallor, with a drop in hemoglobin from 8.5 to 7.7 mg/dl. A nasopharyngeal swab for SARS-CoV-2 was collected on the fourth day of the onset of symptoms which qRT-PCR was positive. He was discharged after 3 days. However, 2 months later, he was admit- They all required transfusion of concentrated red blood cells and hospitalization in a reference hospital to care for children with SCD. We studied 37 cases of severe COVID-19, with three SCD patients, corresponding to 8.1% of all studied cases. All the SCD patients present SNPs, which draws our attention, why we wrote this report. We want to stimulate further studies to draw attention to the possible impact in children with SCD, COVID-19, and SNPs in the TLR pathway. 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